tbuckley/cabot-search huggingface dataset:
Comparison of four clinical prognostic scores in patients with advanced gastric and esophageal cancer.
Authors: Lucy Xiaolu Ma, Osvaldo Espin-Garcia, Yvonne Bach, Hiroko Aoyama, Michael J Allen, Xin Wang, Gail Elizabeth Darling, Jonathan Yeung, Carol Jane Swallow, Savtaj Singh Brar, Patrick Veit-Haibach, Sangeetha Kalimuthu, Rebecca KS Wong, Eric Xueyu Chen, Grainne M. O'Kane, Raymond Woo-Jun Jang, Elena Elimova
Journal: Journal of Clinical Oncology (2022)

4057 Background: While several clinical scoring systems exist to aid prognostication and patient (pt) selection for clinical trials in oncology, none are standardly used. We compared the ability of four prognostic scores to predict overall survival (OS) in pts with advanced gastric and esophageal (GE) cancer. Methods: Pts with advanced (unresectable or metastatic) GE cancer receiving first-line palliative-intent systemic therapy at the Princess Margaret Cancer Centre from 2007 to 2020 were included. High prognostic risk pts were identified using four scoring systems: Royal Marsden Hospital (RMH), MD Anderson Cancer Centre (MDACC), Gustave Roussy Immune Score (GRIm-S) and MD Anderson Immune Checkpoint Inhibitor (MDA-ICI) score. OS was estimated using the Kaplan-Meier method and compared between risk groups (high vs. not-high) for each scoring system using the log-rank test. Cox proportional hazards models were used to analyze the association between each prognostic score and OS, adjusting for baseline clinical factors. Harrell’s c-index was used to evaluate predictive discrimination of the models. Time-dependent AUCs were used to measure predictive ability for early death (within 90 days). Results: In total, 451 pts with advanced GE cancer were included. The median age was 59 years, 68% were male, 51% had ECOG status 0-1, 63% presented with de novo metastatic disease. The proportion of pts categorized as high risk was: RMH 25% (N=113), MDACC 13% (N=95), GRIm-S 24% (N=109), MDA-ICI 26% (N=117). In all scoring systems, high risk pts had significantly shorter OS (median OS 7.9 versus 12.2 months for RMH high vs. low risk, p&lt;0.001; 6.8 vs. 11.9 months p&lt;0.001 for MDACC; 5.3 vs. 13 months p&lt;0.001 for GRIm-S; 8.2 vs. 12.2 months p&lt;0.001 for MDA-ICI). On multivariable analysis, each prognostic score was significantly associated with OS (Table). The GRIm-S had the highest predictive discrimination (c-index 0.645 [0.612-0.678]) and highest predictive ability for early death (AUC 0.754 [0.675-0.832]). Conclusions: All four prognostic scoring systems compared had reasonable accuracy in predicting OS for patients with advanced GE cancer. The higher accuracy for predicting early death may render the GRIm-S as preferable. These tools can aid oncologists in discussions about prognosis, therapeutic decision-making and patient selection for clinical trials.[Table: see text]
Monkeypox: Healthcare workers will be offered smallpox vaccine as UK buys 20 000 doses
Authors: Elisabeth Mahase
Journal: BMJ (2022)

Monkeypox: Healthcare workers will be offered smallpox vaccine as UK buys 20 000 doses Elisabeth MahasePeople with monkeypox should now isolate at home, if they remain well enough, and avoid contact with others until all their lesions have healed and the scabs have dried, the UK Health Security Agency (UKHSA) has said. 1
Novel imaging marker for low- and mid-recurrence score patients at risk for recurrence.
Authors: Joseph R Peterson, Anu K. Antony, The SimBioSys Team, John A. Cole
Journal: Journal of Clinical Oncology (2022)

e12565 Background: The 21-gene (Oncotype DX) recurrence score (RS) has been utilized as a prognostic assay in patients with hormone receptor-positive (HR + ), human epidermal growth factor receptor 2-negative (HER2 - ) breast cancer. The results stratify patients into low-, mid- and high-risk of disease recurrence. Patients with a low recurrence score tend to have lower recurrence rates and are less responsive to chemotherapy. On the other hand, patients with high-recurrence scores are more likely to respond to chemotherapy. While for patients at the high end of the RS spectrum it is apparent that chemotherapy carries benefit, distinguishing chemotherapy benefit for low- and mid-recurrence score (RS-low/-mid) patients is less clear. Methods: To address this, we used a novel 2-paramenter pharmacokinetic modeling framework that allows biosignatures to be extracted from dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) studies that contain 3-6 timepoints spaced 60-90 seconds apart. These parameters, referred to as P1 and P2, represent leakiness from vessels to the extravascular space and vice versa. Results: Using this model, we performed a study in a cohort of 111 breast cancer patients with 21-gene assay RS and DCE-MRIs available. P1 and P2 were extracted from patient standard clinical DCE-MRIs. We performed univariate (Kaplan-Meier) survival analyses to test the prognostic value of the parameters covariate in predicting recurrence free survival (RFS). A pre-specified value of the median P1 and P2 across the patient population was used for stratifying patients into “low” and “high” groups, representing patients with “low” or “high” vessel leakiness. We analyzed patients according to RS. Low P1 showed better outcomes in RS-low and RS-mid patients (n=88, p≤0.028; log-rank test). Patients with a high P1 had a 20.2% chance recurrence at six years. The same trend was observed when considering just RS-mid patients only (n=23, p≤0.058). No recurrences were observed in patients with low P1 in either the RS-low or RS-mid categories. Additionally, there were no recurrences in the high P1, RS-low/-mid category that received chemotherapy, suggesting that chemotherapy could be beneficial in this category of patients, although the trend was not statistically significant (n=10, p=0.46). Similar results were seen for P2. Conclusions: Overall, we demonstrate how our prognostic imaging marker can identify a subset of patients with low-/mid-recurrence scores that could benefit from chemotherapy. This new prognostic approach has the potential to optimize treatment and improve personalized care by providing clarity on the use of chemotherapy in low-/mid-recurrence score patients.[Table: see text]
Outcomes of sintilimab plus pemetrexed and platinum (SPP) according to stage of disease in patients (pts) with locally advanced or metastatic nonsquamous NSCLC (AMnsqNSCLC) in the phase 3 ORIENT-11 study.
Authors: Yunpeng Yang, Zhehai Wang, Jian Fang, Qitao Yu, Baohui Han, Shundong Cang, Gongyan Chen, Xiaodong Mei, Zhixiong Yang, Victoria Jennifer Stefaniak, David Raymond Ferry, Yumin Zhao, Shuyan Wang, Yan Wang, Luyao Sun, Li Zhang
Journal: Journal of Clinical Oncology (2022)

e21157 Background: In ORIENT-11, first-line (1L) SPP improved progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and duration of response (DoR) compared with placebo plus pemetrexed-platinum (PPP) in pts with AMnsqNSCLC. We report outcomes from ORIENT-11 (NCT03607539) for pts treated with SPP with stage III (b &amp; c) compared with stage IV disease. Methods: Pts with treatment-naïve locally AMnsqNSCLC without sensitizing EGFR/ALK alterations were randomly assigned to SPP (n = 266) or PPP (n = 131), stratified by PD-L1 expression, platinum-chemotherapy and sex. Primary endpoint was PFS (RECIST v1.1). Secondary endpoints included OS, ORR, DoR and safety. Kaplan-Meier method was used to analyze median PFS, OS and DoR. Stratified Cox model was used to analyze the hazard ratio (HR) of SPP vs. PPP. Clopper-Pearson method was used to calculate the 95% confidence intervals (CI) of ORR for each group. Miettinen-Nurminen method was used to analyze 95% CI of ORR difference between SPP and PPP. Data cutoff for OS data was September 15, 2021, providing a median follow-up of 30.8 months. Cutoff for other data was November 15, 2019, providing a median follow-up of 8.9 months. Results: 21 pts (7.9%) receiving SPP had stage III disease and 245 pts (92.1%) had stage IV disease. Baseline sex, age and PD-L1 expression ≥1% were similar between subgroups (Table). There were differences between subgroups in number of pts receiving carboplatin and ECOG performance status at baseline. PFS, OS, ORR and DoR outcomes were comparable between pts with stage III and stage IV disease based on the ad-hoc analyses. Any-grade adverse events (AEs) (100.0% vs. 99.6%) and AEs of Grade ≥3 (57.1% vs. 62.0%) were similar in pts with stage III and stage IV disease. Conclusions: In ORIENT-11, outcomes for pts receiving SPP as 1L therapy in AMnsqNSCLC with stage III and stage IV disease were comparable. Clinical trial information: NCT03607539. [Table: see text]
Impact of site-specific metastases and clinical complications on outcomes of patients with metastatic renal cell carcinoma (mRCC).
Authors: Jianbo Wang, Ning Zhang, Sharon H. Giordano, Nizar M. Tannir, Jianjun Gao
Journal: Journal of Clinical Oncology (2022)

e16527 Background: Prognostic models based on the heterogeneity of mRCC disease characteristics, including anemia, hypercalcemia, and neutrophilia, are routinely used in clinic. In an attempt to improve these models, we conducted a retrospective analysis of patients(pts) with mRCC to assess the association of overall outcomes with specific sites of metastasis (mets) and clinical complications. Methods: We extracted data from the SEER-Medicare database on pts diagnosed with RCC from 2004 to 2015. Study cohorts included patients who were &gt; 65 years old and had at least 1 of following site-specific mets or complications: ascites, bone mets, brain mets, liver mets, lung mets, pancreatic mets, and hypercalcemia. To accurately delineate the relationship between site-specific/clinical complications and clinical outcomes, pts were stratified into 3 groups by the timing of site-specific mets and complications appearance : A1 (pts with a site-specific mets or complication at the initial diagnosis of mRCC); A2 (pts with a site-specific mets or complication any time after diagnosis of mRCC); and B (pts who have no site-specific mets or complication but have other mets or complications). Kaplan-Meier curves for overall survival(OS) were produced and median(m) OS were reported. Multivariable Cox modeling was performed to assess the association of individual mets or complications with OS between pre-specified subgroups(A1+A2 vs B, A1 vs A2+B and A1 vs B). Results: We identified 4640 RCC pts in the SEER-Medicare database who had at least 1 of the specified sites of mets or complications. At a median follow-up of 8 months(mons), ascites, brain mets and hypercalcemia were associated with worse mOS in all predefined subgroup analysis. In pts with liver mets, groups A1+A2 had shorter OS than B . In pts with lung mets, mOS in A1 was longer than in A2+B or B. bone mets did not show a statistically significant correlation with OS in any stratified analysis. Lastly, pancreatic mets was associated with longer mOS, but this did not reach statistical significance regardless of the comparison groups (table 1). Conclusions: Our data show that ascites, brain mets, hypercalcemia, and liver mets was associated with poor prognosis, and de novo lung mets was associated with better clinical outcome in patients with mRCC. Based on these findings, we are working on comparing the clinical outcome of mRCC pts treated with targeted therapy to that of pts treated with immunotherapy and building a new prognostic model.[Table: see text]
OTHR-32. The Pediatric Targeted Therapy 2.0 registry: robust molecular diagnostics for precision oncology
Authors: Jonas Ecker, Florian Selt, Dominik Sturm, Martin Sill, Andrey Korshunov, David Capper, Steffen Hirsch, Nicola Dikow, Christian Sutter, Carina Müller, Romain Sigaud, Andreas von Deimling, Kristian W Pajtler, Cornelis M van Tilburg, David T W Jones, Felix Sahm, Stefan M Pfister, Olaf Witt, Till Milde
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The Pediatric Targeted Therapy (PTT) 2.0 program was established to enable precision oncology for relapsed pediatric oncology patients by performing a set of molecular analyses on tumor samples to improve diagnostic accuracy and to detect actionable alterations. METHODS: International pediatric oncology patients with relapse or progression after standard of care treatment independent of histological diagnosis were included. Required material was an FFPE sample from any disease episode available to perform a DNA methylation array, customized targeted gene panel sequencing (130 genes), RNA Sanger sequencing in selected cases, and a pathway-specific immunohistochemistry (IHC) panel. For sequencing a blood sample was used as paired constitutional DNA, allowing for detection of potential cancer predisposition syndromes. All molecular results were discussed in an interdisciplinary tumor board and reported back to the submitting centers. The clinical impact of reported findings was assessed by a serial questionnaire-based two year follow-up. RESULTS: n=266 patients were registered, the molecular workup was successfully performed for n=263 (99%) patients. The most frequent diagnostic category was central nervous system tumors (n=172/263, 65%). Integrated molecular diagnostics suggested a refined or changed diagnosis in n=95/172 (55%) brain tumors. Actionable targets were detected in n=106/172 (61%) cases. In n=11/155 (7.1%) of brain tumor patients pathogenic or likely pathogenic constitutional DNA variants with clinical relevance were identified, n=5 (45%) of which were previously unknown. Clinical follow-up of revealed that n=11/131 (12%) of brain tumor patients received mechanism-of-action based treatment matched to the molecular findings in PTT2.0. CONCLUSIONS: Molecular diagnostics adds robust and clinically relevant information on diagnosis, actionable alterations, and cancer predisposition syndromes in CNS and other pediatric tumors even when tissue from the current disease episode is limited.
INSP-05. Development of fast cortical rhythms in health and mental disease
Authors: Ileana Hanganu-Opatz
Journal: Neuro-Oncology (2022)

Abstract Synchronization of neuronal activity in fast oscillatory rhythms is a commonly observed feature in the adult cerebral cortex. While its exact functions are still a matter of debate, oscillatory activity in gamma frequency range (20-100 Hz) has been proposed to organize neuronal ensembles and to shape information processing in cortical networks. Gamma activity emerges from reciprocal interactions between excitatory and inhibitory neurons. A fine-tuned balance between excitatory drive and inhibitory feedback is mandatory for circuit function underlying cognitive performance, whereas imbalance between excitation and inhibition and resulting gamma disruption have been proposed to cause cognitive disabilities in psychiatric disorders. Despite extensive investigation of gamma activity in adult brain, its development and function early in life are still poorly understood. The talk will highlight recent experimental findings that uncover the mechanisms and role of fast oscillatory activity throughout development. We will uncover how different neuronal populations interact to generate gamma oscillations. Moreover, we will show that these early oscillations are necessary for the adult cognitive abilities. On the flip side, poorer mnemonic and social abilities that have been characterized in several psychiatric disorders, such as schizophrenia and autism, might result from developmental miswiring of the brain. Our data support this hypothesis by demonstrating that weaker fast oscillatory rhythms, sparser connectivity and lower communication are present in the core circuit of cognitive processing, including the prefrontal cortex, hippocampus and entorhinal cortex, in mouse models of these disorders. Together, these findings highlight the relevance of fast cortical rhythms early in life for the adult brain function.
Effect of obesity on time to progression in patients with resectable and potentially resectable pancreatic cancer.
Authors: Palash Asawa, Urwat Til Vusqa, Rahul Karna, Abraham Attah Attah, Ryan Sweeney, Shivani Shah, Thejus Jayakrishnan, Srividya Srinivasamaharaj, Yazan Samhouri, Dulabh K. Monga
Journal: Journal of Clinical Oncology (2022)

e16246 Background: Obesity has been identified as a risk factor for pancreatic cancer. The prevalence of obesity has been on a rise in the last two decades. Obesity is defined by the world health organization (WHO) as body mass index (BMI) &gt; 30.0 kg/m 2 . Studies have shown obese patients to have worse survival than non-obese patients with pancreatic cancer. However, there is limited data on effect of obesity on disease progression. We sought to identify the relationship between obesity and time to progression in patients with resectable and potentially resectable pancreatic ductal adenocarcinoma (PDAC). Methods: We performed a retrospective review of charts of all patients diagnosed with PDAC from 2017-2019 at Allegheny Health Network. Demographics (including age, sex, and race), treatment details, and time to progression date of diagnosis (rounded off in months) were obtained. Two-sided Mann-Whitney U test and Fischer’s exact test were used to evaluate differences between groups with continuous and categorical variables respectively. Furthermore, paired t test was used to compare mean time to progression between the patients in the obese and non-obese groups. A p-value of &lt; 0.05 was considered as level of significance. Results: Out of the 121 patients who received treatment at our institution, 40 patients who had resectable or potentially resectable disease and had progression of disease were included in the analysis. The median age of patients was 68. The majority were females (60%), Caucasians (90%), had Stage I (65%) and potentially resectable disease (55%). Around 70% of patients were treated surgically, 80% received chemotherapy and 26% received radiation therapy. Twelve out of 42 patients were obese (27.5%). No difference in patient characteristics including demographics, staging, and treatment characteristics (proportion of patients who received surgery, chemotherapy, and radiotherapy) was identified between obese and non-obese group patients. The mean time to progression was 11.9 months in obese group as compared to 13.7 months in non-obese group (p = 0.63). Conclusions: Our study showed no significant difference in time to progression of disease between obese and non-obese patients with resectable/potentially resectable pancreatic cancer. Our study is limited by its small sample size, retrospective nature, and unidentifiable confounding factors that could potentially affect outcomes. Larger scale studies are needed to investigate the effect of obesity as a prognostic factor for disease progression in patients with pancreatic cancer.
Characteristics of disease course in patients with locally advanced primarily inoperable HER2-negative breast cancer.
Authors: Natalia Yu. Samaneva, Liubov Yu Vladimirova, Anna E. Storozhakova, Elena A. Kalabanova, Sergey N. Kabanov, Anna V. Tishina, Yakha S. Gaysultanova, Maria A. Teplyakova, Aza A. Lyanova, Natalia A. Abramova, Ludmila A. Ryadinskaya, Irina A. Udalenkova, Natalia M. Tikhanovskaya, Irina L. Popova, Marina M. Sergeeva, Larisa N. Vashchenko
Journal: Journal of Clinical Oncology (2022)

e13072 Background: Breast cancer (BC) is the most common cancer in women worldwide. The purpose of the study was to analyze immediate and long-term results of treatment in patients with locally advanced primarily inoperable HER2-negative breast cancer depending on the time of progression. Methods: The study included 104 women with locally advanced primarily inoperable HER2-negative breast cancer who developed an early disease progression within 6 to 12 months after standard combination treatment. The blood levels of circulating tumor cells (CTCs) were measured in all patients during the progression stage. Results: An analysis of the overall (OS) and event-free (EFS) survival showed that median EFS in patients with luminal B subtype was 9 months, in patients with triple-negative (TNBC) subtype 8 months. EFS at 6 months was 87.5% in luminal B subtype and 79.4% in TNBC, p = 0.37985. Median OS in patients with luminal B subtype was 25 months, in patients with TNBC 26 months. One-year OS was 100% in luminal B subtype and 93.9% in TNBC, p = 0.138. 2-year OS was 54.2% in luminal B subtype and 55.9% in TNBC, p = 0.697. 3-year OS was 37.5% in luminal B subtype and 41.2% in TNBC, p = 0.639. CTCs were detected in all patients, with higher levels in patients with luminal B subtype than in TNBC patients. HER+ CTCs were found in 30% of patients with luminal B subtype but not registered in patients with TNBC. Such results were obtained for the first time. Conclusions: The absence of significant differences demonstrated the aggressive disease course in patients with luminal BC with identified primary hormone resistance, similar to the TNBC course. The results should be taken into account when predicting the course of the disease and developing further treatment tactics.
Influence of type 2 diabetes mellitus and concomitant anti-diabetic medications in patients with metastatic pancreatic ductal adenocarcinoma.
Authors: Andrea Pretta, Erika Cimbro, Riccardo Giampieri, Dario Spanu, Eleonora Lai, Federica Pecci, Francesca Balconi, Alessio Lupi, Marta Pozzari, Sara Murgia, Fabio Bardanzellu, Antonio Maccioni, Fabiana Contu, Mara Persano, Clelia Donisi, Valeria Pusceddu, Marco Puzzoni, Pina Ziranu, Rossana Berardi, Mario Scartozzi
Journal: Journal of Clinical Oncology (2022)

e16301 Background: The association between pancreatic ductal adenocarcinoma (PDAC) and type 2 diabetes mellitus (DM2) has long been evaluated. Indeed, DM2 can be both an epiphenomenon of PDAC and a risk factor. However, the data on the influence of DM2 and concomitant drug therapy in the progression of pancreatic neoplasms are conflicting. The present study aimed to investigate the correlation between overall survival (OS) and antidiabetic drugs in patients with metastatic pancreatic ductal adenocarcinoma and DM2. Methods: Data from 232 patients were collected retrospectively from 2014 to 2021. 174 from the Department of Medical Oncology of the University Hospital of Cagliari and 58 from the Department of Medical Oncology, AOU Ospedali Riuniti of Ancona. All patients had stage IV disease and received gemcitabine plus nab-paclitaxel first-line chemotherapy. Statistical analysis was performed with the MedCalc package. We aimed to evaluate the correlation between DM2, anti-diabetic medications (ADMs) and median overall survival (mOS). Survival distribution was assessed by Kaplan-Meier curves. Finally, multivariate analysis was performed, taking into consideration the following prognostic factors: sex, ECOG-PS, LDH, Ca19.9, and metastatic sites. Results: The median age was 69 y.o. (range 40-84 y.o.), 127 (54,7%) were male. All patients received first-line treatment with gemcitabine plus nab-paclitaxel. 138 (59,4%) patients were not affected by DM2, 94/232 (40,6%) were affected by DM2. Among DM2 patients, 57 (%) were insulin-treated and 37 (%) were metformin-treated. DM2 patients showed a statistically significant higher median overall survival (26 versus 11 months, 95% CI, p = 0,0002). Furthermore, among DM2 patients insulin-treated and metformin-treated showed a mOS of 21 months and 33 months, respectively (95% CI, p = 0.0002). Finally, multivariate analysis showed that treated-DM2 is an independent prognostic factor ( p = 0.03). Conclusions: The results of our study showed a correlation between DM2 on treatment (with insulin or metformin) and higher mOSin patients with metastatic PDAC. However, the limitations due to retrospective data collection must be considered. The mechanisms underlying these findings could be explained by maintaining optimal insulin concentration and good glycemic control during treatments, or by the activity of anti-diabetic medication in neoplastic tissues. However, further studies in this setting are needed.